One of the most active areas in current oncological research involves the study of the role of the endocrine system in cancer. Oncogenesis at a variety of sites is thought to be due to an endocrine imbalance, and analysis of estrogen receptor status of neoplasms is becoming increasingly important in therapeutic manipulations of many tumors. It has been known for many years that estradiol concentrates in tissues which possess high concentrations of estrogen receptors. Recently, several investigators have taken advantage of this property of compounds which bind to estrogen receptors to design and synthesize radiohalogenated estrogen receptor binding radiotracers which concentrate in tumors which possess estrogen receptors and which may provide a means for non-invasively determining the estrogen receptor status of these tumors via imaging techniques. The goal of this project is to develop Tc-99m complexes which localize in estrogen dependent tumors as a result of high affinity binding to estrogen receptors. The approach taken involves the synthesis of bifunctional compounds which consist of a stable, neutral, lipid soluble, Tc-99m complex covalently attached to a molecule known to bind with high affinity to estrogen receptors. Analogs of both 17-Beta-estradiol and hexestrol will be synthesized. In vitro receptor binding assays will be performed using estrogen receptors isolated from the uteri of immature female Wistar rats. Those Tc-99m complexes which are found to bind avidly to estrogen receptors will be studied in vivo. Biodistribution studies will be performed in immature female Wistar rats to determine if the Tc-99m complex localizes in the uterus which is rich in estrogen receptors. Repeat studies using estradiol to block estrogen receptors will be done in the same animal model to demonstrate estrogen receptor mediated uptake of the Tc-99m complex by the uterus. Those compounds which are found to localize in the uterus will then be evaluated in C57B1/6 mice bearing the MXT mouse mammary carcinoma to determine if estrogen receptor specific Tc-99m complexes are potentially useful as tumor imaging agents in humans.